We are in the process of evaluating the long-term effects of desferal chelation therapy on patients with transfusional iron overload. Most of these patients have thalassemia major, but other diseases which require chronic transfusions are also being treated by continuous subcutaneous desferal therapy. We are monitoring cardiac, liver and endocrine functioning as well as iron excretion in all of the patients under our protocol. A second phase of our efforts is aimed at determining the most efficacious methods for preparing young red cells for transfusion. Young red cells (neocytes) have longer life expectancies than older cells, and when transfused into chronically transfused patients, increase the interval between transfusions by approximately 80%. This diminution is directly equivalent to the decrease in iron accumulated from the red cell transfusion. When combined with the removal of old cells, gerocytes, patients accumulate iron at a significantly slower rate. Such modifications should allow oral chelating agents to become significant chelators and should normalize the lifespan of the patients.